Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection

Bodéus, Monique; Hubinont, Corinne; Bernard, Pierre; Bouckaert, A.; Thomas, Karl; Goubau, Patrick

doi:10.1002/(sici)1097-0223(199904)19:4<314::aid-pd542>3.0.co;2-h

Cited by 118 publications

(57 citation statements)

References 16 publications

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“…There are literature reports of false negative and false positive results, but some of these studies are based on old cases, and culture and molecular techniques have been greatly improved since. Moreover, we always perform amniocentesis after 21 WG and at least 6 weeks after the presumed date of maternal infection to lower the risk of false negatives, as described by Bodeus et al 9 This very good reliability of amniotic fluid analysis is a major point: a negative amniotic fluid analysis reassures the providers and the parents that the fetus is at low risk of an adverse outcome. Ultrasound sensitivity and specificity have often been debated, 27 but the quality of US is increasing, and knowledge of fetal anatomy and diseases is also improving.…”

Section: Discussionmentioning

confidence: 99%

A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome

et al. 2013

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Objective To analyze the outcome of maternal primary cytomegalovirus (CMV) infection.Methods Retrospective analysis of a cohort of 238 patients with maternal primary CMV infection detected at routine screening. The cases were managed with serial ultrasound (US) scans, and amniocentesis was performed in 36.1% of cases. All prenatal results were confirmed at birth. ResultsThe average age was 31.9 (18-44) years. Patients were symptomatic in 21% of cases. The rate of intrauterine transmission was 24.9%, and it was 8.8%, 19%, 30.6%, 34.1% and 40% in the preconceptional period, the periconceptional period, and the first, second and third trimesters of pregnancy, respectively (p = 0.025). There was a significantly higher risk of US abnormalities when maternal infection occurred during the preconceptional or periconceptional period and the first trimester compared with later (p < 0.001). Because of US abnormalities, pregnancy was terminated in 18 cases at the parents' request. Three infected newborns were symptomatic; all three cases were suspected at US before birth. We did not observe any symptomatic fetal infection when maternal infection occurred after 14 weeks of gestation. A number of clinically asymptomatic cases (5.5%) developed hearing loss. ConclusionThe rate of materno fetal transmission is linearly correlated to the gestational age at infection. No severe case of congenital infection was observed if maternal infection occurred after 14 weeks of gestation.

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confidence: 99%

A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome

et al. 2013

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“…Proposed diagnostic algorithms have focused on first-trimester screening, since the time of infection can be accurately obtained in the absence of seroconversion data, and the clinical sequelae of congenital CMV is usually more severe if transmission occurs early in gestation (30,48). A high positive predictive value (PPV) and NPV for clinical disease have been determined for quantitative PCR testing of amniotic fluid (26); however, there is an increased risk of a false-negative result if fewer than 7 weeks have elapsed between the onset of maternal infection and the time of amniocentesis (5,36). In addition, amniotic fluid testing prior to 21 weeks gestation only has a 30 to 45% sensitivity rate, while testing after 21 weeks gestation increases the sensitivity to 74% (13,35).…”

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Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

et al. 2005

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No single diagnostic test for cytomegalovirus (CMV) infection is currently available for pregnant women at all stages of gestation. Improved accuracy in estimating the timing of primary infections can be used to identify women at higher risk of giving birth to congenitally infected infants. A diagnostic algorithm utilizing immunoglobulin G (IgG), IgM, and IgG avidity was used to prospectively screen serum from 600 pregnant women enrolled from two groups: <20 weeks gestation (n ‫؍‬ 396) or >20 weeks gestation (n ‫؍‬ 204). PCR testing of urine and/or blood was performed on all seropositive women (n ‫؍‬ 341). The majority (56.8%) of women were CMV IgG seropositive, with 5.5% being also CMV IgM positive. In the IgM-positive women, 1.2% had a low-avidity IgG, indicating a primary CMV infection and a high risk of intrauterine transmission. Two infants with asymptomatic CMV infection were born of mothers who had seroconverted in the second trimester of pregnancy. Baseline, age-stratified CMV serostatus was established from 1,018 blood donors. Baseline seropositivity from a blood donor population increased with age from 34.9% seroprevalence at less than 20 years of age to 72% seroprevalence at 50 years of age. Women at high risk of intrauterine transmission of CMV were identified at all stages of gestation. Women infected with CMV during late gestation may be more likely to transmit the virus, so failure to detect seroconversions in late gestation may result in failure to detect infected neonates.Human cytomegalovirus (CMV) is the most common cause of congenital malformation resulting from viral intrauterine infection in developed countries (12,21,48). Primary CMV infection occurs in 0.15 to 2.0% of all pregnancies and may be transmitted to the fetus in up to 40% of cases (48). Up to 15% of intrauterine CMV infections result in symptomatic congenital disease at birth, and 10 to 15% of those born with asymptomatic congenital CMV will develop significant clinical sequelae in infancy (7,10,18). In utero transmission of CMV can occur during primary maternal infection, reactivation, or reinfection of seropositive mothers. Most concern centers on primary maternal infection, due to the potential for significant fetal damage when the infection is acquired and transmitted during the first trimester (30, 48). Perinatal infections can result through virus transmission from many parts of the birth canal (39); however, the majority of these infections are asymptomatic (43).The usefulness of prenatal testing for CMV has been questioned due to the absence of clearly effective intervention (1, 27) and to evidence for severe congenital malformation resulting from viral reactivation (6,8,20). Continuing advancements in technology, however, mean reliable and inexpensive serologic tests are available, prenatal diagnostic procedures with acceptable negative predictive values (NPV) can be performed, and trials of neonatal antiviral treatments are ongoing (25,34,37,50,52). Proposed diagnostic algorithms have focused on first-trimester screeni...

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“…Moreover, the direct detection of viral components, including pp65 antigenemia and DNAemia, can be helpful for acute infection diagnosis. Prenatal diagnosis of HCMV congenital infection relies on virus isolation from amniotic fluid (AF) and/or viral DNA detection by PCR in AF samples (4,12,24,25,36,42). In a previous study, we reported that the combination of culture and PCR on AF samples allows a reliable prenatal diagnosis, with 72% sensitivity and 97.6% specificity (18).…”

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Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples from Mothers with Primary Infection

Gault²,

et al. 2002

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A real-time PCR assay was developed to quantify human cytomegalovirus (HCMV) DNA in amniotic fluid (AF) samples collected from 30 pregnant women with primary HCMV infection as detected either from HCMV-immunoglobulin G (IgG) seroconversion or by the presence of HCMV-specific IgG and IgM associated with a low IgG avidity. Clinical information available for each case included ultrasonographic examination and fetal or newborn outcome. HCMV infection of fetuses or newborns was confirmed for the 30 studied cases. AF samples were subdivided into three groups. In group A (n ‫؍‬ 13), fetuses presented major ultrasound abnormalities, and pregnancy was terminated. In group B (n ‫؍‬ 13), fetuses had normal ultrasound findings, the pregnancy went to term, and the newborns were asymptomatic at birth. In group C (n ‫؍‬ 4), fetuses had no or minor ultrasonographic signs, and pregnancy was terminated. The HCMV DNA load values in AF samples were significantly higher in group A (median, 2.8 ؋ 10 5 genome equivalents [GE]/ml) than in group B (median, 8 ؋ 10 3 GE/ml) (P ‫؍‬ 0.014). Our findings suggest that HCMV load level in AF samples correlates with fetal clinical outcome but might also be dependent on other factors, such as the gestational age at the time of AF sampling and the time elapsed since maternal infection.Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection in developed countries, affecting 0.5 to 2% of all live births (1,32,40). Although the possibility of severe symptomatic fetal infection following recurrent maternal infection has been reported (8), fetal damage is mostly related to primary maternal infection (16,38,39). In this case, the transmission of the virus to the fetus may occur in 20 to 50% of pregnancies (18,27,38). It has been reported that HCMV transmission rates increase with gestational age and that a major risk of transmission is observed for seroconversion occurring late in pregnancy (5).Congenitally infected infants are asymptomatic at birth in about 90% of cases, and for symptomatic infants, infection ranges from mild to severe disseminated life-threatening disease resulting in up to 20% perinatal mortality (9,16,22,28,31,37). Up to 90% of the surviving symptomatic newborns will exhibit psychomotor and perceptual sequelae such as sensorineural hearing loss, mental retardation, cerebral palsy, seizures, and visual defects (2). Additionally, 10% of the infants who are asymptomatic at birth will later develop complications, mainly neurodevelopmental defects and deafness (7,15,40).The diagnosis of maternal primary HCMV infection is based mostly on serological testing, including HCMV immunoglobulin G (IgG) seroconversion and the presence of specific HCMV IgG and IgM (35). Moreover, the direct detection of viral components, including pp65 antigenemia and DNAemia, can be helpful for acute infection diagnosis. Prenatal diagnosis of HCMV congenital infection relies on virus isolation from amniotic fluid (AF) and/or viral DNA detection by PCR in AF samples (4,12,24,25,36,42)...

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Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection

Cited by 118 publications

References 16 publications

A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome

A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome

Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples from Mothers with Primary Infection

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